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Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles

Delivery of macromolecular drugs to the brain is impeded by the blood brain barrier. The recruitment of leukocytes to lesions in the brain, a typical feature of neuroinflammation response which occurs in cerebral ischemia, offers a unique opportunity to deliver drugs to inflammation sites in the bra...

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Autores principales: Zhang, Chun, Ling, Cheng-li, Pang, Liang, Wang, Qi, Liu, Jing-xin, Wang, Bing-shan, Liang, Jian-ming, Guo, Yi-zhen, Qin, Jing, Wang, Jian-xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595130/
https://www.ncbi.nlm.nih.gov/pubmed/28900508
http://dx.doi.org/10.7150/thno.19979
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author Zhang, Chun
Ling, Cheng-li
Pang, Liang
Wang, Qi
Liu, Jing-xin
Wang, Bing-shan
Liang, Jian-ming
Guo, Yi-zhen
Qin, Jing
Wang, Jian-xin
author_facet Zhang, Chun
Ling, Cheng-li
Pang, Liang
Wang, Qi
Liu, Jing-xin
Wang, Bing-shan
Liang, Jian-ming
Guo, Yi-zhen
Qin, Jing
Wang, Jian-xin
author_sort Zhang, Chun
collection PubMed
description Delivery of macromolecular drugs to the brain is impeded by the blood brain barrier. The recruitment of leukocytes to lesions in the brain, a typical feature of neuroinflammation response which occurs in cerebral ischemia, offers a unique opportunity to deliver drugs to inflammation sites in the brain. In the present study, cross-linked dendrigraft poly-L-lysine (DGL) nanoparticles containing cis-aconitic anhydride-modified catalase and modified with PGP, an endogenous tripeptide that acts as a ligand with high affinity to neutrophils, were developed to form the cl PGP-PEG-DGL/CAT-Aco system. Significant binding efficiency to neutrophils, efficient protection of catalase enzymatic activity from degradation and effective transport to receiver cells were revealed in the delivery system. Delivery of catalase to ischemic subregions and cerebral neurocytes in MCAO mice was significantly enhanced, which obviously reducing infarct volume in MCAO mice. Thus, the therapeutic outcome of cerebral ischemia was greatly improved. The underlying mechanism was found to be related to the inhibition of ROS-mediated apoptosis. Considering that neuroinflammation occurs in many neurological disorders, the strategy developed here is not only promising for treatment of cerebral ischemia but also an effective approach for various CNS diseases related to inflammation.
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spelling pubmed-55951302017-09-12 Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles Zhang, Chun Ling, Cheng-li Pang, Liang Wang, Qi Liu, Jing-xin Wang, Bing-shan Liang, Jian-ming Guo, Yi-zhen Qin, Jing Wang, Jian-xin Theranostics Research Paper Delivery of macromolecular drugs to the brain is impeded by the blood brain barrier. The recruitment of leukocytes to lesions in the brain, a typical feature of neuroinflammation response which occurs in cerebral ischemia, offers a unique opportunity to deliver drugs to inflammation sites in the brain. In the present study, cross-linked dendrigraft poly-L-lysine (DGL) nanoparticles containing cis-aconitic anhydride-modified catalase and modified with PGP, an endogenous tripeptide that acts as a ligand with high affinity to neutrophils, were developed to form the cl PGP-PEG-DGL/CAT-Aco system. Significant binding efficiency to neutrophils, efficient protection of catalase enzymatic activity from degradation and effective transport to receiver cells were revealed in the delivery system. Delivery of catalase to ischemic subregions and cerebral neurocytes in MCAO mice was significantly enhanced, which obviously reducing infarct volume in MCAO mice. Thus, the therapeutic outcome of cerebral ischemia was greatly improved. The underlying mechanism was found to be related to the inhibition of ROS-mediated apoptosis. Considering that neuroinflammation occurs in many neurological disorders, the strategy developed here is not only promising for treatment of cerebral ischemia but also an effective approach for various CNS diseases related to inflammation. Ivyspring International Publisher 2017-07-23 /pmc/articles/PMC5595130/ /pubmed/28900508 http://dx.doi.org/10.7150/thno.19979 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhang, Chun
Ling, Cheng-li
Pang, Liang
Wang, Qi
Liu, Jing-xin
Wang, Bing-shan
Liang, Jian-ming
Guo, Yi-zhen
Qin, Jing
Wang, Jian-xin
Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title_full Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title_fullStr Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title_full_unstemmed Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title_short Direct Macromolecular Drug Delivery to Cerebral Ischemia Area using Neutrophil-Mediated Nanoparticles
title_sort direct macromolecular drug delivery to cerebral ischemia area using neutrophil-mediated nanoparticles
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595130/
https://www.ncbi.nlm.nih.gov/pubmed/28900508
http://dx.doi.org/10.7150/thno.19979
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